This is about cardiac health and not BC. I post it because it is unusually unequivocal in its statements on the benefits of omega 3s.

It seems to me that anything that assists with cardiac health is good news; it would be nice if they looked to see if omega 3s helped reduce any cardiac implications of Herceptin.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Am J Clin Nutr. 2008 Jun;87(6):1991S-6S.
Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death.
Mozaffarian D.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Department of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA, USA. dmozaffa@hsph.harvard.edu

Large observational studies, randomized clinical trials, and experimental studies have evaluated the effects of fish and n-3 fatty acid consumption on fatal coronary heart disease (CHD) and sudden cardiac death (SCD), clinically defined events that most often share the final common pathway of fatal ventricular arrhythmia. These different study designs, each having complementary strengths and limitations, provide strong concordant evidence that modest consumption of fish or fish oil (1-2 servings/wk of oily fish, or approximately 250 mg/d of EPA+DHA) substantially reduces the risk of CHD death and SCD. Pooled analysis of prospective cohort studies and randomized clinical trials demonstrates the magnitude and dose-response of this effect, with 36% lower risk of CHD death comparing 0 and 250 mg/d of EPA+DHA consumption (P < 0.001), but then little additional benefit with higher intakes. Reductions in risk are even larger in observational studies utilizing tissue biomarkers of n-3 fatty acids that more accurately measure dietary consumption. The concordance of findings from different studies also suggests that effects of fish or fish oil on CHD death and SCD do not vary depending on presence or absence of established CHD. The strength and consistency of the evidence, and the magnitude of this effect are each notable. Because more than one-half of all CHD deaths and two-thirds of SCD occur among individuals without recognized heart disease, modest consumption of fish or fish oil, together with smoking cessation and regular moderate physical activity, should be among the first-line treatments for prevention of CHD death and SCD.

RB,

Thanks for this.

Do I remember you posting some helpful relationship between Omega 3's and Auto-Immune disease?

THX

TRS

Tsund - thanks for the thanks,

I do not recall doing so, but there may have been a post that was looking at inflammation that also considered auto immune conditions.

Here are two trials that suggest that fish oil / Omegas 3 may assist reduce the risk of auto immune conditions.

RB


http://www.jacn.org/cgi/content/full/21/6/495

Journal of the American College of Nutrition, Vol. 21, No. 6, 495-505 (2002)
Published by the American College of Nutrition
REVIEW
Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases
Artemis P. Simopoulos, MD, FACN

The Center for Genetics, Nutrition and Health, Washington, D.C

Abstract

"There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs."


http://www.ncbi.nlm.nih.gov/pubmed/11802309
Isr Med Assoc J. 2002 Jan;4(1):34-8.Links
n-3 fatty acids and the immune system in autoimmunity.
Ergas D, Eilat E, Mendlovic S, Sthoeger ZM.

Department of Internal Medicine B, Kaplan Medical Center, Rehovot, Israel. ergaz@clalit.org.il

"Therefore, the use of n-3 fatty acids can be recommended to the general healthy population, not only to prevent atherosclerosis but possibly also to reduce the risk of autoimmunity."

(I re-copied this to this thread as it is significant I suspect)


It all interconnects - what happy coincidences - The post on MS by Bill, and Hopeful of an MMP9 all come together at the same moment in a search for an article on MMP9 omega six and gene expression.

Conclusion Omega 3 suppresses MMP-9 which is a marker of MS and BC

http://www.springerlink.com/content/963788775224p348/

"The treatment with both ω-3 PUFA and fish oil dose-dependently inhibited the LPS-induced production of MMP-9. Our results suggest that a low fat diet supplemented with ω-3 PUFA may become recommended for the well being of MS patients under therapy."

MMP9 has been on my list of interest. I do not know exactly what it is, but saw a trial a long time ago that I will dig out that suggested the omega 3 and 6 significantly change gene expression of MMP9. I have been wondering ever since about MMP 9.



This was posted in articles of interest
http://breastcancersource.com/breast...48_0_0_0.aspx?
2 June 2008
Urine biomarker test confirms breast cancer precursor lesions
MedWire News: Matrix metalloproteinases can be detected in the urine of women with atypical breast hyperplasia and could form the basis for an accurate and convenient test for invasive breast cancer risk, researchers claim.

"Once validated in larger studies, such a test could potentially provide a useful adjunct for breast cancer risk assessment," Marsha Moses (Harvard Medical School, Boston, Massachusetts, USA) and colleagues comment, adding: "The goal of identifying women at high risk of developing breast cancer and providing safe effective risk reduction to this group is compelling."

Matrix metalloproteinases are required for the "angiogenic switch" - an early and critical event in breast cancer growth and progression, Moses et al explain in the journal Cancer Epidemiology, Biomarkers and Prevention.

Matrix metalloproteinase 9 (MMP-9) and a disintegrin and metalloprotease 12 (ADAM 12) are two established serum biomarkers in breast cancer.

More evidence Omega 6 LA is implicated in BC.

And why COX blockers may have an impact as the block these pathways.

And more PGE2 may = more aromatase = more oestrogen products

More oestrogen would result in more conversion of LA to AA the raw material for this process be enhancing long chain fat conversion.

SO this could be a self fuelling tumour loop where Omega 6 is present in excess and there is no Omega 3 to moderate the process.

RB




http://www.springerlink.com/content/n547j2538p317388/

Xin-Hua Liu1, Jeanne M. Connolly1 and David P. Rose1 Contact Information
(1) Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, New York, USA
(2) Division of Nutrition and Endocrinology, American Health Foundation, 10595 Valhalla, NY, USA

Received: 21 August 1995 Accepted: 27 October 1995

Diets rich in linoleic acid (LA) stimulate the metastasis of MDA-MB-435 human breast cancer cells from the mammary fat pads of nude mice. This omega-6 fatty acid is metabolized to various cyclo-oxygenase and lipoxygenase products, several of which have been previously associated with tumor cell invasion and metastasis. We now report that MDA-MB-435 cells secreted increased levels of prostaglandin E2 (PGE2),

Striking figures for COX blockers.

DHA is a cox blocker.

It is suggested COX blockers seek to moderate the downstream effect of excess Omega 6.

So balancing Omega 3s and 6s may assist in any COX blocking based strategy.

Please discuss dietary change with your doctor. The posts are only intended to inform debate.



Chemoprevention of Breast Cancer in Rats by Celecoxib, a Cyclooxygenase 2 InhibitorRandall E. Harris2, Galal A. Alshafie, Hussein Abou-Issa and Karen Seibert

School of Public Health [R. E. H., G. A. A., H. A-I.], Comprehensive Cancer Center [R. E. H., H. A-I.], and Department of Surgery [H. A-I.], The Ohio State University College of Medicine, Columbus, Ohio 43210, and Searle Monsanto Research and Development, St. Louis, Missouri 63137 [K. S


Nonsteroidal anti-inflammatory drugs (NSAIDs) have been observed to reduce the relative risk of breast cancer. This prompted our investigation of the chemopreventive potential of celecoxib, a specific cyclooxygenase 2 blocker, against mammary carcinogenesis induced by 7,12-dimethyl-benz(a)anthracene in female Sprague Dawley rats. Treatment with celecoxib was examined and compared to treatment with the general NSAID, ibuprofen, and to a control group receiving only dimethylbenz(a)anthracene. Dietary administration of celecoxib (1500 ppm) produced striking reductions in the incidence, multiplicity, and volume of breast tumors relative to the control group (68%, 86%, and 81%, respectively; P < 0.001). Ibuprofen also produced significant effects, but of lesser magnitude (40%, 52%, and 57%, respectively; P < 0.001). These results help confirm the chemopreventive activity of NSAIDs against breast cancer and provide the first evidence that a cyclooxygenase 2 blocking agent, celecoxib, possesses strong chemopreventive activity against mammary carcinogenesis.

Cancer therapy for animals

http://www.huntsvillecompounding.com/vet%20cancer.pdf
Gigi Davidson, BSPh, RPh, FSVHP, DICVP
North Carolina State University College of Veterinary Medicine
Raleigh, North Carolina

"Matrix metalloproteinases (especially MMP-2 and MMP-9) are
enzymes that are secreted to degrade the ECM. Any new blood
vessels formed by angiogenesis can migrate only after the ECM is
degraded. MMP-2 and MMP-9 have long been associated with
tumor progression and metastasis.6-8 Although mechanisms of MMP
inhibition remain obscure, n-3 omega fatty acids have been shown
to be very effective MMP inhibitors,"

Very largely outside my reading but another mechanism by which Omega 3s may reduce the risk of BC.

RB

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

1: Cancer Res. 2008 Apr 15;68(8):2912-9.Click here to read Links
Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells.
Sun H, Berquin IM, Owens RT, O'Flaherty JT, Edwards IJ.

Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against breast cancer but biochemical mechanisms are unclear. Our studies showed that the n-3 fatty acid docosahexaenoic acid (DHA) up-regulated syndecan-1 (SDC-1) in human breast cancer cells, and we tested the hypothesis that DHA-mediated up-regulation of SDC-1 induces apoptosis. DHA was delivered to MCF-7 cells by n-3 PUFA-enriched low-density lipoproteins (LDL) or by albumin in the presence or absence of SDC-1 small interfering RNA. The n-3 PUFA induced apoptosis, which was blocked by SDC-1 silencing. We also confirmed that SDC-1 up-regulation and apoptosis promotion by n-3 PUFA was mediated by peroxisome proliferator-activated receptor gamma (PPAR gamma). Using a luciferase gene driven by either a PPAR response element or a DR-1 site present in the SDC-1 promoter, reporter activities were enhanced by n-3 LDL, DHA, and PPAR gamma agonist, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. Cotransfection with dominant-negative PPAR gamma DNA eliminated the increase in luciferase activity. These data provide strong evidence that SDC-1 is a molecular target of n-3 PUFA in human breast cancer cells through activation of PPAR gamma and that n-3 PUFA-induced apoptosis is mediated by SDC-1. This provides a novel mechanism for the chemopreventive effects of n-3 PUFA in breast cancer.

PMID: 18413760 [PubMed - indexed for MEDLINE]

WOW - you cannot argue with measured fats in breast tissue, - they do not have momentary memory lapses about what people ate, - they do not respond to very short term dietary changes - they simply and accurately reflect diet.

For me this is powerful evidence that Omega 6 and 3 have a role in the risk of breast cancer occurrence.

The bold and underline are mine.

RB



"We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect."




Nutr Cancer. 2002;42(2):180-5.

http://www.ncbi.nlm.nih.gov/pubmed/12416257?ordinalpos=1&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.P ubmed_Discovery_RA&linkpos=2&log$=relatedarticles& logdbfrom=pubmed

Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer.
Bagga D, Anders KH, Wang HJ, Glaspy JA.

Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, USA.

Animal studies suggest that dietary polyunsaturated fatty acids (PUFAs) of the n-6 class, found in corn and safflower oils, may be precursors of intermediates involved in the development of mammary tumors, whereas long-chain (LC) n-3 PUFAs, found in fish oil, can inhibit these effects. This case-control study was designed to examine the relationship between the PUFA composition of breast adipose tissue and the risk of breast cancer. Using fatty acid levels in breast adipose tissue as a biomarker of past qualitative dietary intake of fatty acids, we examined the hypothesis that breast cancer risk is negatively associated with specific LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) and positively associated with n-6 PUFAs (linoleic acid and arachidonic acid). Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined by gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates while adjusting for age. The age-adjusted n-6 PUFA (linoleic acid and arachidonic acid) content was significantly higher in cases than in controls (P = 0.02). There was a trend in the age-adjusted data suggesting that, at a given level of n-6 PUFA, LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) may have a protective effect (P = 0.06). A similar inverse relationship was observed with LC n-3-to-n-6 ratio when the data were adjusted for age (P = 0.09). We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect.

There are a number of trials with chemo drugs suggesting synergies with long chain Omega 3.

It is something obviously to discuss with your medical adviser before altering your diet.

If you want to search for your particular chemo combinations try entering the drug and DHA or EPA or Omega 3 and see what comes up. You could always take the result along with you to show your advisors. http://www.ncbi.nlm.nih.gov/

Here they are suggesting Omega 3 may effect Her2. [ In an other trial it has been shown Omega 3 and 6 change Her2 gene expression by significant amounts in rat skeletal muscular tissue.]

Trials on other cancers suggest that DHA may increase rates of cell death. In healthy cells long chain omega 3s may be protective and some reports suggest an antioxidant effect - and DHA seems to have a part to play in defective cell kill off. It is very complicated and I only post these views through the thick mist so you understand that DHA is OK for healthy cells - dolphins would be in trouble otherwise (-: with all the fish they eat.


http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

J Nutr Biochem. 2008 Jul 3. [Epub ahead of print]Click here to read Links
The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy.
Biondo PD, Brindley DN, Sawyer MB, Field CJ.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5.

Dietary intake of long-chain omega-3 (or n-3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) can affect numerous processes in the body, including cardiovascular, neurological and immune functions, as well as cancer. Studies on human cancer cell lines, animal models and preliminary trials with human subjects suggest that administration of EPA and DHA, found naturally in our diet in fatty fish, can alter toxicities and/or activity of many drugs used to treat cancer. Multiple mechanisms are proposed to explain how n-3 PUFA modulate the tumor cell response to chemotherapeutic drugs. n-3 PUFA are readily incorporated into cell membranes and lipid rafts, and their incorporation may affect membrane-associated signaling proteins such as Ras, Akt and Her-2/neu. Due to their high susceptibility to oxidation, it has also been proposed that n-3 PUFA may cause irreversible tumor cell damage through increased lipid peroxidation. n-3 PUFA may increase tumor cell susceptibility to apoptosis by altering expression or function of apoptotic proteins, or by modulating activity of survival-related transcription factors such as nuclear factor-kappaB. Some studies suggest n-3 PUFA may increase drug uptake or even enhance drug activation (e.g., in the case of some nucleoside analogue drugs). Further research is warranted to identify specific mechanisms by which n-3 PUFA increase chemotherapy efficacy and to determine the optimal cellular/membrane levels of n-3 PUFA required to promote these mechanisms, such that these fatty acids may be prescribed as adjuvants to chemotherapy.

Omega Six The Devils Fat

I have written a book that looks at the impact of EXCESS Omega 6 and lack of Omega 3 on health and behaviour. The subject has become a passion. It will be the diet subject of the next decade. The book is very much less technical than these posts. It is not light reading but has been understood by women from 20 to 80 who have absolutely no technical medical or scientific background. Even self confessed "non readers" have been sufficiently intrigued to spend the time to look at it, once they have dipped into the book.

The material specifically on breast cancer is no where near as comprehensive as this thread, and the book is very much wider, but helps you get a wider perspective of why this is such an important health topic and how it all fits together.

You can read a few pages on Amazon and my web site.

This is a subject that is particularly fundamental to women as women make 10 times as much DHA as men do. DHA is fundamental to women's health and arguably helps define what it is to be a woman.

"GOSH I didn't know that" an expression of genuine surprise and interest, is a generic common reaction of women to some of the material.

The message is simple balance the Omega 3s and 6s. To really appreciate why it is so important you really need to understand a little of why. There are lighter books but this one should leave you in no doubt how important the correct balance of EFAs is to mental and physical health at every level.

WWW.omegasixthedevilsfat.com

http://www.amazon.com/Omega-Six-Devi...5959567&sr=1-1

http://www.amazon.co.uk/Omega-Six-De...5959501&sr=1-1

Tilapia (fish) fats discussion on NPR
 

Hi Robert,

I heard this report this weekend on the radio, and thought I'd mention it for consideration:

http://www.npr.org/rss/podcast.php?id=510284

(Look for the July 11, 2008 report)

Re Talapia - Thanks AA interesting that the subject of excess Omega 6 is making the main stream.

INFLAMMATION - Excess omega 6 and lack of omega 3 promotes inflammation in the body.

It is becoming more and more evident that inflammation is a big factor in the cancer process.

These are some fascinating links that make that point.

http://www3.interscience.wiley.com/j...22663/abstract

ABSTRACT
"In this review I would like to show the evidence that tumor development and progression are accelerated inevitably by inflammation caused from foreign bodies, and that reactive oxygen species derived from inflammatory cells are one of the most important genotoxic mediators to accelerate the process."

http://www3.interscience.wiley.com/j...22662/abstract

ABSTRACT
"Infection and chronic inflammation contribute to about 1 in 4 of all cancer cases. Mediators of the inflammatory response, e.g., cytokines, free radicals, prostaglandins and growth factors, can induce genetic and epigenetic changes including point mutations in tumor suppressor genes, DNA methylation and post-translational modifications, causing alterations in critical pathways responsible for maintaining the normal cellular homeostasis and leading to the development and progression of cancer."

http://www3.interscience.wiley.com/j...22664/abstract

ABSTRACT
" A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. "



http://www3.interscience.wiley.com/j...22661/abstract

http://her2support.org/vbulletin/sho...d=1#post167964

This is a link to Robins fascinating thread on activation of HER2 by a virus (EBV), and inhibition of that virus by long chain Omega 3s.

I thought it was worth re posting here for completeness.

RB

Complicated but interesting.

Prostaglandins and leukotrienes are products of Omega Six.

It is an interesting suggestion that CLA may inhibit the downstream products of Omega 6. But as ever it is easier to cut down on excess Omega Six and balance with 3s, so avoiding excess Omega 6 products in the first place.

RB



Proliferative responses of normal human mammary and MCF-7 breast cancer cells to linoleic acid, conjugated linoleic acid and eicosanoid synthesis inhibitors in culture

Anticancer Research (Greece) , 1997, 17/1 A (197-203)

Potential mechanisms for the stimulation or inhibition of cell growth by linoleic acid (LA) and conjugated linoleic acid (CLA) were investigated by using eicosanoid linoleic acid (CLA) were investigated by using eicosanoid synthesis inhibitors. Normal human mammary epithelial cells (HMEC) and MCF-7 breast cancer cells were incubated in serum-free medium supplemented with LA or CLA and cyclooxygenase (indomethacin; INDO) or lipoxygenase (nordihydroguaiaretic acid; NDGA) inhibitors. Linoleic acid stimulated the growth and (3H)thymidine incorporation of normal HMEC and MCF-7 cancer cells, while CLA was inhibitory. Supplementation with LA increased intracellular lipid peroxide concentrations in normal HMEC and MCF-7 cancer cells, whereas CLA did not affect lipid peroxide formation. Normal HMEC and MCF-7 cells supplemented with LA and INDO or NDGA resulted in growth inhibition. The treatment of normal HMEC with CLA and INDO or NDGA, and MCF-7 cells with CLA and INDO stimulated cell growth. However, the addition of CLA and NDGA to MCF-7 cells resulted in synergistic growth suppression suggesting that CLA effects were mediated through lipoxygenase inhibition. Although NDGA was more inhibitory of cell growth in the presence of LA or CLA than INDO, growth was associate with both prostaglandin and leukotriene production. Additional studies are warranted to elucidate the mechanism(s)

whereby LA or CLA affect breast cell growth.

RB - I've mentioned that I am working on helping heal my best friends lymphadema and also have been working very hard on fixing my iron over load in my liver. I grew eating the Mediterranean diet , as both my parents are from Greece. I never had a tv dinner or frozen food until I lived on my own in my 20's. Fast food was unheard of in my household. We only had "spaceburgers" or Jack in the Box the night we decorated the Christmas tree and Chinese in the restaurant on New Years. We fished and clammed all summer and ate our fish in the winter, grew our own veggies and picked our own fruit off the apple. cherry, pear, peach plum and quince trees (native to the Island of Create and my back yard). My mom cooked dandelion, and lentil soups from scratch. The only soup I ever ate from a can was tomato and everything was cooked in olive oil.

I have strayed over the years from a clean diet and paid the price. I have from time to time went back to the old ways, but have strayed many times over. Since becoming sick I have added supplements and herbs to my Mediterranean diet. This time around (the last 2 -3 months) I have really payed attention to everything going in to my body and when (because of my sugar level). The omega's are really important as are the anti-inflammatory herbs and spices. I have scanned your information because I can't always get my head in to reading and retaining information, but I will read it again. Thanks for all the information. This diet has really helped me get my liver functions under control and reducing the iron in my blood.

Another mechanism by which long chain Omega 3 blocks BC, this time through BRAC1.



1: Oncol Rep. 2007 Apr;17(4):713-9.Click here to read Links
Increased BRCA1 protein in mammary tumours of rats fed marine omega-3 fatty acids.
Jourdan ML, Mahéo K, Barascu A, Goupille C, De Latour MP, Bougnoux P, Rio PG.


INSERM, E 0211; Université François Rabelais; CHU Bretonneau, Tours, F-37000, France.

Any factor affecting BRCA gene regulation may be of interest in the prevention of breast tumourigenesis. We studied the influence of dietary docosahexaenoic acid (DHA), a major omega-3 fatty acid present in marine products, on rat autochthonous mammary tumourigenesis. DHA-supplementation significantly reduced the incidence of tumours (30%, P=0.007) and led to a 60% increase (P=0.02) in BRCA1 protein level. Since DHA influences the product of a major tumour suppressor gene, this finding may contribute to the observation that high-fish consumption reduces the risk of breast cancer.

The current issue (Aug. 18/Aug. 25) of US News and World Report has an arrticle - "Making Sense of the Omega Fat Puzzle" by Sarah Baldaug and a health column by Bernadine Healy, former Director of NIH, entitled "From Fish Oil to Medicine".

Dr. Healy says that "... though eating fatty fish is the way to go, refined fish oil supplements with specified doses of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) can make for a more certain prescription, and one that alleviates concerns about fish being contaminated with mercury or PCBs. (Nasty fish burps can be avoided by freezing the gel capsules and taking them at bedtime.) "

Omega-6 fats cause prostate tumors to grow twice as fast
 

http://www.universityofcalifornia.edu/news/article/7839

Omega-6 fats cause prostate tumors to grow twice as fast
Email this article
Date: 2006-02-01
Contact: Steve Tokar
Phone: (415) 221-4810
Email: steve.tokar@med.va.gov
Omega-6 fatty acids--such as those found in corn oil--caused human prostate tumors in cell culture to grow twice as quickly as tumors to which omega-6 fats had not been added, according to a study conducted at the San Francisco VA Medical Center.

An omega-6 fatty acid known as arachidonic acid turns on a gene signaling pathway that leads directly to tumor growth, according to principal investigator Millie Hughes-Fulford, PhD, director of the Laboratory of Cell Growth at SFVAMC and scientific advisor to the U.S. Under Secretary for Health for the Department of Veterans Affairs.

The results of the study are published in the February 1 issue of Cancer Research.

"After we added omega-6 fatty acids to the growth medium in the dish, and only omega-6, we observed that tumors grew twice as fast as those without omega-6," recounts Hughes-Fulford, who is also an adjunct professor of medicine at the University of California, San Francisco.

"Investigating the reasons for this rapid growth, we discovered that the omega-6 was turning on a dozen inflammatory genes that are known to be important in cancer. We then asked what was turning on those genes, and found that omega-6 fatty acids actually turn on a signal pathway called PI3-kinase that is known to be a key player in cancer," she adds.

Hughes-Fulford says the results are significant because of the high level of omega-6 fatty acids in the modern American diet, mostly in the form of vegetable seed oils such as corn oil-over 25 times the level of beneficial omega-3 fatty acids, which are found in canola oil, fish, and green vegetables. She notes that over the last 60 years, the rate of prostate cancer in the U.S. has increased steadily along with intake of omega-6, suggesting a possible link between diet and prostate cancer.

The study results build on earlier work in which Fulford and her research team found that arachidonic acid stimulated the production of an enzyme known as cPLA-2, which in turn caused a chain of biochemical reactions that led to tumor growth. In the current paper, the researchers have "followed that biochemical cascade upstream to its source," Hughes-Fulford says. "These fatty acids are initiating the signal pathway that begins the whole cascade."

Hughes-Fulford and her fellow researchers also found that if they added a non-steroidal antiflammatory or a PI3K inhibitor to the growth media, interrupting the signal pathway, the genes did not get turned on and increased tumor cell growth did not take place.

Currently, Hughes-Fulford is conducting a study in which research animals are fed diets with different levels of omega-3 and omega-6 fatty acids, "to see how the tumors grow in animals."

Hughes-Fulford says that her study results have directly influenced her own diet. "I'm not a physician, and do not tell people how to eat, but I can tell you what I do in my own home," she says. "I use only canola oil and olive oil. We do not eat deep-fried foods."

Co-authors of the study include Chai-Fei Li, BA, of the Northern California Institute for Research and Education, J.B. Boonyaratanakornkit, BS, of SFVAMC and UCSF, and Sina Sayyah, BA, of NCIRE.

The study was funded by grants from the Department of Veterans Affairs and a grant from NASA that was administered by NCIRE.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in health care, and providing complex patient care.

This looks like a fascinating and informative paper. I have not paid to view it but part is available at the lower link.

Definitely worth at least a skim if you have the time.

It emphasises the importance of the Omega 3:6 ratio in breast cancer risk, and in one place suggests a need for a ration of around 1:1 or 1:2 Omega 3 :6.

http://www.ncbi.nlm.nih.gov/pubmed/16145262

http://books.google.co.uk/books?hl=e...HJLU#PPA147,M1

The omega 3:6 balance, inflammation, COX 2 pathways and downstream products are factors in BC.

See also COX 2 posts.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum




1: Nutr Cancer. 2007;59(1):14-20.Links
Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer.
Cerchietti LC, Navigante AH, Castro MA.

Translational Research Unit, Angel H Roffo Cancer Institute, Universidad de Buenos Aires, Buenos Aires, Argentina. lcerchie@aecom.yu.edu

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.

RB- what is celecoxib? A Cox2 inhibitor of some sort I assume?

And, do you think this would applicable to mom who suffers multiple immune system problems, probably stemming from her chronic leukemia, along with muscle wasting/fibromylagia.
Thanks

TRS

Hi T Sund

Here is a link for celecoxib.

http://en.wikipedia.org/wiki/Celebrex

I cannot in any way give advice on specific conditions in relation to individual circumstances. I have no training to do so. I can only draw your attention to the generality of relevant trials for your consideration.

Omega 3 and 6 do impact on the immune function through a number of mechanisms. IF there is dietary excess of Omega 6 and a lack of Omega 3 fats from plant sources (eg vegetable oils) AND a lack of long chain Omega 3s DHA and EPA or blocked conversion pathways there is significant evidence this can negatively impact on the immune function.

As posted already there is some evidence that increasing the intake of long chain omega 3s may help in some circumstances with fatigue etc.

These are listed as symptoms of CFS

http://www.spineuniverse.com/display...rticle155.html

Symptoms of Fibromyalgia include:

—Multiple tender points and muscle pain

—Disturbed sleep with morning fatigue and stiffness

—Aggravation of signs and symptoms by modulating factors (emotional stress, temperature changes)

—Subjective swelling and numbness

—Chronic headaches

—Irritable bowel syndrome

—Cold intolerance (Raynaud's Phenomenon)

—Dysmenorrhea - painful menstruation

—Exercise intolerance

—Weakness

A number of them have also been linked at some level with Omega 3:6 imbalances.


A search under leukemia or CFS and DHA or Omega 3 etc on Pubmed http://www.ncbi.nlm.nih.gov/ will produce some trials.


CFS
There are a few for CFS. This is an example suggesting CFS sufferers have a lack of Omega 3 and excess Omega 6

Neuro Endocrinol Lett. 2005 Dec;26(6):745-51.Links
In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.
Maes M, Mihaylova I, Leunis JC.

M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Antwerp, Belgium.

ABSTRACT

"There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things- --omega3 PUFAs, such as EPA and DHA."

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

So have a look at some more.

LEUKEMIA

There has been some work in the area of leukemia which seems to suggest possible benefits for EPA for example or usage as a treatment adjunct.

http://www.ncbi.nlm.nih.gov/sites/en...20%20omega%203


GOOD CLINICAL BOOK ON ACUTE INFLAMMATION

This is expensive but an excellent book you could give to your doctor. It is rare in being clinically orientated It is a powerful book. It is not an easy read but your friend just needs to get the jist and give it to her doctor as a basis for dietary discussion.

Omega 3 Fatty Acids in Clinical Nutrition by Heller, Stehr and Koch.

AND FINALLY

Your friend must tell to her doctor before any significant change in diet. I would suggest doing some more reading on Omega 3 and 6 and CFS etc printing the information and taking it to the doctor at the time of visit.

Another mechanism by which Omega 6 linoleic acid induces tissue formation , migration and proliferation.

Oxidised Omega 6 linoleic acid induces rapid dose dependent upregulation of Syndecan-4

http://www.ncbi.nlm.nih.gov/pubmed/16636895

Breast Cancer Res Treat. 2006 Jul;98(1):91-8. Epub 2006 Apr 25.Click here to read Links
Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype.
Baba F, Swartz K, van Buren R, Eickhoff J, Zhang Y, Wolberg W, Friedl A.

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA.

Members of the syndecan and glypican families of cell surface heparan sulfate proteoglycans (HSPGs) are modulators of growth factor signaling and cell adhesion. Both loss and gain in expression of syndecans and glypicans has been associated with malignant progression. The goal of this project was to investigate a possible relationship between expression of cell surface HSPGs (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1, syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone receptor (PR). Clinical follow-up information was available for up to 18.6 years (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma cells ranged from complete loss to high expression, but glypican-1 was detected only in a small subset of breast carcinomas. Expression of all three HSPGs was significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025; syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1 expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS: p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify syndecan-1 as an independent prognostic marker, which was due to its significant association with established prognostic factors. The strong association between cell surface HSPGs and the Ki67 proliferation marker would support a biologic role in carcinoma growth regulation. Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype.

http://www.asco.org/ASCO/Abstracts+&...tractID=202291



Specific Induction of Syndecan-4 in Vascular Endothelial Cells of Breast Cancer - Implications for FGF-2-Induced Angiogenesis.
Sub-category:


Proc Am Soc Clin Oncol 19: 2000 (abstr 2603)
Author(s):

Christoph Mundhenke, Sally Drew, Zhen Chang, Aung Choon, Andreas Friedl
Abstract:

Introduction: Fibroblast growth factor-2 (FGF-2) is a potent angiogenic stimulator. Binding of FGF-2 to its receptor tyrosine kinases (RTKs) and cellular signaling are modulated by heparan sulfate proteoglycans (HSPGs) via their heparin-like heparan sulfate (HS) side chains. HS can be specific positive or negative regulators of FGF signaling depending on their ability to bind to both FGF ligand and RTK. Aim: The goal of this study was to localize different cell surface HSPGs in breast cancer and normal breast tissue and to examine their roles in FGF signaling. Materials and Methods: HSPGs were detected immunohistochemically in paraffin embedded tissues using antibodies directed against the HSPG core proteins of glypican-1, syndecan-1 and syndecan-4. The ability of HSPGs to promote FGF-2 signaling complex assembly was tested by using FGF-2 ligand and soluble RTK fusion protein (FR1-AP) as binding probes (Chang et al. FASEB J., in press). Results: HSPGs are induced in the stroma of infiltrating carcinomas in a striking tissue compartment and cell type-specific fashion. Syndecan-4 is dramatically induced in activated endothelial cells within infiltrating carcinoma tissue, while endothelial cells in normal breast gland are syndecan-4 negative. Syndecan-1 is strongly up-regulated in fibroblasts within the desmoplastic stroma surrounding infiltrating cancer cells. Glypican-1 is found in stromal fibroblasts in the immediate vicinity of cancer cells. FGF-2 binds to HSPGs in all stromal compartments. FR1-AP binds to FGF-2 immobilized on stromal fibroblast and endothelial cell HSPGs, suggesting, that syndecan-1 on fibroblasts and syndecan-4 on endothelial cells promote FGF-2 signaling complex assembly. Summary: Syndecan-4 is induced in tumor vessel endothelial cells of infiltrating carcinomas of the breast, facilitating FGF-2 signaling and thereby likely promoting angiogenesis.




http://ajpcell.physiology.org/cgi/co...ull/288/2/C458
ABSTRACT

Syndecan-4, a heparan sulfate proteoglycan that is widely expressed in the vascular wall and as a cell surface receptor, modulates events relevant to acute tissue repair, including cell migration and proliferation, cell-substrate interactions, and matrix remodeling. While syndecan-4 expression is regulated in response to acute vascular wall injury, its regulation under chronic proatherogenic conditions such as those characterized by prolonged exposure to oxidized lipids has not been defined. In this investigation, arterial smooth muscle cells were treated with 13-hydroperoxy-9,11-octadecadienoic acid (HPODE) and 13-hydroperoxy-10,12-octadecadienoic acid, oxidized products of linoleic acid, which is the major oxidizable fatty acid in LDL. Both oxidized fatty acids induced a dose-dependent, rapid upregulation of syndecan-4 mRNA expression that was not attenuated by cycloheximide. This response was inhibited by pretreatment with N-acetylcysteine, catalase, or MEK1/2 inhibitors, but not by curcumin or lactacystin, known inhibitors of NF-{kappa}B. These data suggest that oxidized linoleic acid induces syndecan-4 mRNA expression through the initial generation of intracellular hydrogen peroxide with subsequent activation of the extracellular signal-regulated kinase signaling pathway via MEK1/2. Notably, the HPODE-induced enhancement of syndecan-4 mRNA was accompanied by accelerated shedding of syndecan-4. In principle, alterations in both the cell surface expression and shedding of syndecan-4 may augment a variety of proatherogenic events that occur in response to oxidized lip

PPAR gamma has made a previous appearance as having a link with BC. The trial below suggest that the products of oxidation of Omega 6 linoleic acid promote PPAR gamma which is suggested to be a tumour promoter in BC.



http://genesdev.cshlp.org/cgi/content/abstract/18/5/528

ABSTRACT

"These results suggest that once an initiating event has taken place, increased PPAR{gamma} signaling serves as a tumor promoter in the mammary gland."


http://carcin.oxfordjournals.org/cgi...act/24/11/1717

ABSTRACT

Activation of PPAR {gamma} in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR {gamma}

Arthur W. Bull1,4, Knut R. Steffensen2, Jörg Leers2 and Joseph J. Rafter3

1 Oakland University, Department of Chemistry, Rochester MI 48309-4477, USA, 2 Center for Biotechnology, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden and 3 Department of Medical Nutrition, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) {gamma} plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for {gamma}1, {gamma}2 and {gamma}3, in Caco-2 and HCT-116 colon cell lines showed that {gamma}3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR {gamma} by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR {gamma}1 or {gamma}2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR {gamma} and that PPAR {gamma} plays an important role in the differentiation of intestinal cells.

Linoleic Acid-Induced VCAM-1 Expression in Human Microvascular Endothelial Cells Is Mediated by the NF-κβ-Dependent Pathway
Authors: Hyen Joo Park; Yong Woo Lee; Bernhard Hennig; Michal Toborek
DOI: 10.1207/S15327914NC41-1&2_18
Publication Frequency: 6 issues per year
Published in: journal Nutrition and Cancer, Volume 41, Issue 1 & 2 September 2001 , pages 126 - 134


Abstract
Vascular cell adhesion molecule-1 (VCAM-1) has been reported to play an important role in cancer metastasis via the adhesive interaction between tumor cells and endothelial cells. In this study, we examined the effects of linoleic acid on VCAM-1 expression and its transcriptional regulatory mechanism in human microvascular endothelial cells (HMEC-1). Time- and dose-dependent increases of VCAM-1 mRNA levels were observed in linoleic acid-treated HMEC-1 as detected by reverse transcriptase-polymerase chain reaction. Flow cytometry analysis showed a significant and dose-dependent upregulation of VCAM-1 expression in HMEC-1 stimulated with linoleic acid compared with controls. To clarify the transcriptional regulatory pathway, we investigated the role of nuclear factor-κβ (NF-κβ) in the expression of VCAM-1 by linoleic acid in HMEC-1. Nuclear extracts from HMEC-1 stimulated with linoleic acid showed a dose-dependent increase in binding activity to the NF-kB consensus sequences. These effects were preventable by cotreatment with inhibitors of NF-κβ activity, such as sodium salicylate, aspirin, or pyrrolidine dithiocarbamate. In addition, pretreatment with NF-κβ inhibitors markedly suppressed the ability of linoleic acid to induce VCAM-1 gene expression. The role of NF-κβ in linoleic acid-induced VCAM-1 expression was confirmed by functional promoter studies in HMEC-1 transfected with reporter constructs of the VCAM-1 promoter with or without mutated NF-κβ binding site. These results indicate that linoleic acid upregulates VCAM-1 expression in HMEC-1 through the NF-κβ-dependent pathway.

Fat -1 is a gene in worms that converts omega 6 to omega 3. Animals and humans do not have that ability.

They have done trial where they insert the gene into pigs and mice and they make Omega 6 into Omega 3 and tend to balance the two.

Here they are seeing what happens to cancer cells if the fat gene is inserted into cancer cells and the cells put into mice.

The fat gene inhibited cell proliferation in prostate cancer.

In essence once again a balance of Omega 3s and 6s / lower Omega 6s may help inhibit cancer.

RB



Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3{beta} phosphorylation.
Lu Y, Nie D, Witt WT, Chen Q, Shen M, Xie H, Lai L, Dai Y, Zhang J.

Department of Medicine, University of Pittsburgh, VA Pittsburgh Healthcare Systems, Room 2E146, University Drive, Pittsburgh, PA 15240. zhangj2@upmc.edu.

Epidemiologic studies inclusively indicate that "unhealthy" dietary fat intake is one of the potential risk factors for cancer. In dietary fat, there are two types of polyunsaturated fatty acids (PUFA), omega-3 (n-3) and omega-6 (n-6). Numerous studies support that the ratio of n-6/n-3 affects tumorigenesis. It was reported that adenoviral transfer of the fat-1 gene, which converts n-6 to n-3, into breast and lung cancer cells had an antitumor effect in vitro. However, the effects of the fat-1 gene expression on tumor growth in vivo have not been studied and the mechanisms remain unclear. Accordingly, prostate cancer DU145 and PC3 cells were transfected with either the fat-1 gene or a control vector. The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector. The fat-1 gene expression significantly inhibited prostate cancer cell proliferation and invasion in vitro. The fat-1 and control vector-transfected prostate cancer cells were s.c. implanted into severe combined immunodeficient mice for 6 weeks. The fat-1 gene expression significantly diminished tumor growth in vivo, but the control vector had no effect. Finally, we evaluated signaling pathways that may be important for fat-1 gene function. Administration of n-3 PUFA induced caspase-3-mediated prostate cancer cell apoptosis in vitro. The fat-1 gene expression inhibited prostate cancer cell proliferation via reduction of GSK-3beta phosphorylation and subsequent down-regulation of both beta-catenin and cyclin D1. These results suggest that fat-1 gene transfer directly into tumor cells could be used as a novel therapeutic approach. [Mol Cancer Ther 2008;7(10):3203-11].

Arachidonic acid is the long chain Omega 6 and raw material of the Omega 6 chemicals. COX 2 is one of the enzymes that converts arachidonic acid to its down stream products.

This is another confirmation of a link between oestrogen production and Omega 6.

The vegetable based Omega 6 increases COX 2 expression.

The only place you can get Omega 6 is in the diet you cannot make it.

Long chain Omega 3 has a blocking effect on COX2 Omega 6 products by a variety of mechanisms.


RB



Cyclooxygenase-2 mRNA expression correlates with aromatase expression in human breast cancer.
Salhab M, Singh-Ranger G, Mokbel R, Jouhra F, Jiang WG, Mokbel K.

St. George's University of London, Tooting, London, United Kingdom.

INTRODUCTION: The cyclooxygenase-2 (COX-2), responsible for the conversion of arachidonic acid into prostaglandin (PG) E2, is known to increase intracellular cAMP and estrogen production in malignant breast tissue. The aromatase enzyme complex is responsible for local production of estrogens in breast cancer. Increasing evidence supports a role for COX-2 in upregulation of aromatase activity. The aim of this study was to examine the relationship between COX-2 and aromatase mRNA expression in human breast cancer. METHODS: A total of 160 breast samples (127 tumor tissues and 33 normal tissues) were analyzed. Levels of transcription were determined using real-time quantitative PCR. COX-2 and aromatase mRNA expression were normalized against CK19. Levels of expression of COX-2 were correlated with those of aromatase using Pearson's correlation method. RESULTS: Levels of expression of COX-2/CK19 of both benign and malignant tissues were positively correlated with aromatase/CK19 transcript levels (correlation coefficient = +0.536, P < 0.0001). When we compared levels of expression of both genes in malignant samples only, there was a highly significant positive correlation (r = +0.611, P < 0.00001). CONCLUSION: This study demonstrates a strong positive relationship between COX-2 and aromatase mRNA expression, and lends further support to the hypothesis that COX-2 is an upregulator of aromatase in breast tissue.

1: Breast Cancer Res Treat. 2007 Jan;101(1):7-16. Epub 2006 Jul 6.Click here to read Links
Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells.
Hammamieh R, Chakraborty N, Miller SA, Waddy E, Barmada M, Das R, Peel SA, Day AA, Jett M.

Division of Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, MD 20910, USA.

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (omega-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (omega-3) EFA as anti-oncogenic factors. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the omega-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of omega-3 and omega-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with omega-3 and omega-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of omega-3 and omega-6EFAs.

Changing your Omega 3 6 intake shows up quite quickly in breast tissue (3 months).

It take about 680 day to change half of your adipose fat.

Fats in blood change quite quickly but still reflect stored Omega 6.

The body heavily stores Omega 6 (Omega 6 is 3-30% of body fat dependent on the amount in the diet) but stores very little Omega 3 (Omega 3 is usually under 1% of body fat and in the West often a fraction of a percent).

Omega 6 increases the risk of cancer and Omega 3s reduce the risk of cancer.

Does concentration of Omega 6 in the breast where the diet is high in Omega 6 could explain why breasts are more susceptible to cancer than part of the body that are less reliant on Omega 3 and 6..

These patients were given 1.8 gram EPA and 1.2 grams DHA a day. The full trial is free.

http://jnci.oxfordjournals.org/cgi/reprint/89/15/1123




Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.
Bagga D, Capone S, Wang HJ, Heber D, Lill M, Chap L, Glaspy JA.

Department of Medicine, School of Medicine, University of California at Los Angeles, 90095-6956, USA.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

This is technical and relates to pancreatic cancer and not BC (although it mentions it) and posted for specialists who keep an eye on this thread if any.

But the pathways under discussion are so basic there is undoubtedly some communality, as in the impact of COX blockers like aspirin in BC.

Linoleic acid is the plant based Omega 6.

A way of reducing Omega 6 COX and LOX activity is not to eat excess Omega 6 in the first place, and Omega 3 DHA has been shown to be a natural COX blocker.

The article gives an idea as to how widespread the effects of the products of Omega 6 are.

Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer
Xian-Zhong Ding,1 Rene Hennig,1 and Thomas E Adriancorresponding author1
1Department of Surgery and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Tarry 4-711, Chicago, IL 60611, U.S.A


http://www.pubmedcentral.nih.gov/art...i?artid=149414


"COX and LOX metabolism of linoleic and arachidonic acids leads to the formation of a variety of metabolically active products with different roles in carcinogenesis. Our understanding of these roles is steadily increasing. This new information is providing a theoretical basis for development of new cancer chemoprevention approaches targeted to COX and LOX activity."

Erythrocyte fatty acids and risk of proliferative and nonproliferative fibrocystic disease in women in Shanghai, China.
Shannon J, King IB, Lampe JW, Gao DL, Ray RM, Lin MG, Stalsberg H, Thomas DB.

Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR.

BACKGROUND: Although benign breast changes are more common than breast cancer, little evidence regarding risk factors for benign breast conditions is available. Omega-3 (n-3) fatty acids have antiinflammatory and antiproliferative actions and may be important in reducing the risk of benign conditions. There is a lack of research on the association of n-3 fatty acids with risk of benign fibrocystic breast changes. OBJECTIVES: The objectives of the study were to evaluate the role of n-3 and other fatty acids in the development of benign proliferative fibrocystic conditions (PFCs) and nonproliferative fibrocystic conditions (NPFCs) in the breast and to evaluate the progression of fibrocystic changes in breast cancer. DESIGN: We conducted a case-control study to determine erythrocyte fatty acid concentrations in 155 women with NPFCs, 185 women with PFCs, 241 women with breast cancer (127 with nonproliferative and 114 with proliferative changes in the noncancerous extratumoral mammary epithelium), and 1030 control subjects. We estimated the relative risk of NPFCs, PFCs, and breast cancer with proliferative and nonproliferative changes in extratumoral tissue compared with the risk of these changes alone. RESULTS: Women in the highest quartile of eicosapentaenoic acid concentrations were 67% less likely to have an NPFC alone or with breast cancer and 49% less likely to have breast cancer than were women with PFCs. gamma-Linolenic acid (18:3n-6) was positively associated with all fibrocystic and cancerous conditions. Palmitic:palmitoleic acid (n-7 saturation index) was inversely associated with risk in all comparisons. CONCLUSION: Our results support a protective effects of n-3 fatty acid intake and the n-7 saturation index against benign fibrocystic breast changes and the progression of proliferative changes to breast cancer.

More on Omega 3s and 6s and BC.
 

ALA is the plant based Omega 3.

Nuts are high in Omega 6, as are many processed foods.

Processed foods may also contain oxidised fats, and be low on antioxidants.

Fruit and veg contain antioxidants.

Again the trial generally underlines the importance of diet.

RB



1: Int J Cancer. 2009 Feb 15;124(4):924-31.Click here to read Links
Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer.
Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Bénichou J, Clavel-Chapelon F.

INSERM, ERI-20, Institut Gustave Roussy, Villejuif Cedex, France.

Experimental studies suggest detrimental effects of omega-6 polyunsaturated fatty acids (PUFA), and beneficial effects of omega-3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow-up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with alpha-linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between omega-6 and long-chain omega-3 PUFAs, with breast cancer risk inversely related to long-chain omega-3 PUFAs in women belonging to the highest quintile of omega-6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk.

Role of fatty acids in malignancy and visual impairment: epidemiological evidence and experimental studies.
Tsubura A, Yuri T, Yoshizawa K, Uehara N, Takada H.

Department of Pathology II, Kansai Medical University, Takii Hospital, Moriguchi, Osaka, Japan. tsubura@takii.kmu.ac.jp

International variation in breast and colon cancer incidence is positively related to total fat intake. However, total fat consists of different fatty acid families, e.g., saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-3 and n-6 polyunsaturated fatty acids (PUFAs). Epidemiological evidence and experimental studies suggest that these fatty acid families have different effects on breast and colon carcinogenesis. Therefore the action of each fatty acid on carcinogenesis should be evaluated separately. Although it is difficult to establish firm conclusions on the effect of each fatty acid in human epidemiological studies, experimental studies on animals and cultured cells suggest that n-6 PUFAs (linoleic acid and arachidonic acid) may have a tumor promoting effect, while n-3 PUFAs (eicosapentaenoic acid, docosahexaenoic acid and alpha-linolenic acid) and conjugated fatty acids (CFAs; a mixture of positional and geometric isomers of PUFAs with conjugated double bonds) exert an inhibitory effect on tumor growth. SFAs such as palmitic acid and stearic acid show little or no tumor promoting effect, and the action of oleic acid, a MUFA, is inconclusive. In addition to regulation of abnormal cell growth seen in cancers, fatty acids also control cell loss seen in degenerative eye diseases, such as degeneration of lens material in cataract and degeneration of photoreceptor cells in retinitis pigmentosa. Experiments suggest that n-6 PUFAs cause deleterious effects, while n-3 PUFAs result in beneficial effects on the lens and retina. In particular, docosahexaenoic acid is known to be effective in rescuing photoreceptor cells from damage. Thus, understanding the function of each fatty acid is likely to be important for making progress in treating these and other diseases.

To correlate breast cancer outcomes with Omega 3: tissue status you arguably need to look at breast fat at the time of biopsy.

This trial suggests central adipose tissue is not a good marker. Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer. (below)

Adipose buttock tissue saves fats differently again and tends to accumulate more Omega 3 and 6, and significant changes are seen in 3 months. http://www.ncbi.nlm.nih.gov/pubmed/11489728

Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer.

For me this throws into question Omega 3:6 trials on breast cancer looking a buttock fat after the event. http://jnci.oxfordjournals.org/cgi/reprint/85/10/785

Fatty Acid Composition of the Subcutaneous
Adipose Tissue and Risk of Proliferative
Benign Breast Disease and Breast Cancer

Breasts are designed to make milk so probably have fat accumulation and conversion rules all of their own, which might make them more susceptible to fat imbalances (more reading required when I have time).


http://grande.nal.usda.gov/ibids/ind...s&therow=81227

Dietary modulation of omega-3/omega-6 polyunsaturated fatty acid ratios in patients with breast cancer.

BACKGROUND: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied. PURPOSE: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements. METHODS: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test. RESULTS: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P less than .0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P less than .0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged. CONCLUSION: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer.
Bagga D, Anders KH, Wang HJ, Glaspy JA.

Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, USA.

Animal studies suggest that dietary polyunsaturated fatty acids (PUFAs) of the n-6 class, found in corn and safflower oils, may be precursors of intermediates involved in the development of mammary tumors, whereas long-chain (LC) n-3 PUFAs, found in fish oil, can inhibit these effects. This case-control study was designed to examine the relationship between the PUFA composition of breast adipose tissue and the risk of breast cancer. Using fatty acid levels in breast adipose tissue as a biomarker of past qualitative dietary intake of fatty acids, we examined the hypothesis that breast cancer risk is negatively associated with specific LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) and positively associated with n-6 PUFAs (linoleic acid and arachidonic acid). Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined by gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates while adjusting for age. The age-adjusted n-6 PUFA (linoleic acid and arachidonic acid) content was significantly higher in cases than in controls (P = 0.02). There was a trend in the age-adjusted data suggesting that, at a given level of n-6 PUFA, LC n-3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) may have a protective effect (P = 0.06). A similar inverse relationship was observed with LC n-3-to-n-6 ratio when the data were adjusted for age (P = 0.09). We conclude that total n-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that LC n-3 PUFAs, derived from fish oils, may have a protective effect.

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France.
Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, Lavillonnière F, Body G, Le Floch O, Chajès V.

Laboratoire de Biologie des Tumeurs, Clinique d'Oncologie-Radiothérapie, Service de Gynécologie-Obstétrique, E.A. 2103, Unité de Recherche Associée Université-INRA, CHU, Tours, France.

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer. Copyright 2001 Wiley-Liss, Inc.

Not as certain as looking at breast tissue but interesting none the less.

A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer.
Wolk A, Bergström R, Hunter D, Willett W, Ljung H, Holmberg L, Bergkvist L, Bruce A, Adami HO.

Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden.

BACKGROUND: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer. METHODS: We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs). RESULTS: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer. CONCLUSIONS: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

Off the track of Omega 3s and 6s but interesting that increased protein decreased risk significantly. It would be interesting to see the whole paper to get a better idea what was going on in their diet, what sort of protein, how it related to fats carbs Omega 3 and 6s etc.


Dietary factors and survival from breast cancer.
Author: Rohan, T E : Hiller, J E : McMichael, A J
Citation: Nutr-Cancer. 1993; 20(2): 167-77

The association between self-reported intake of various dietary factors at diagnosis and survival from breast cancer was studied in a population-based cohort of breast cancer patients in Adelaide, South Australia. These patients had been recruited between 1982 and 1984 into a case-control study of diet and incident breast cancer. Of the 451 patients recruited originally, 412 were followed for a median interval of 5.5 years. There were decreases in the risk of death from breast cancer ranging from 25 to 40% at all levels of energy and protein intake above the baseline, whereas for fat intake there was a 40% increase in risk at the uppermost quintile level. There was also some reduction in risk at the upper levels of intake of beta-carotene and vitamin C. However, there were no dose-dependent variations in risk of death by level of intake for any of the dietary factors studied, and most of the variation in risk that was observed was relatively insubstantial.

Melatonin / Omega 6 linolenic acid / BC
 

Melatonin is an very powerful antioxidant and is an Omega 6 inflammatory chemical blocker.

Found as usual whilst looking for something else.(-:

Melatonin production in general terms falls post menopause. Obesity and poor sleep are associated with lower melatonin.

Application of melatonin improved mood and reduced depression in post menopausal women.

Depressed melatonin has been noted in some cancers.

Melatonin
By S. R. Pandi-Perumal, Daniel P. Cardinali
http://books.google.com/books?id=m_6...efox-a#PPR7,M1



RB



http://cancerres.aacrjournals.org/cg...ct/65/23/11174

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats


The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 µW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 µW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.

David E. Blask1, George C. Brainard2, Robert T. Dauchy1, John P. Hanifin2, Leslie K. Davidson1, Jean A. Krause1, Leonard A. Sauer1, Moises A. Rivera-Bermudez3, Margarita L. Dubocovich3, Samar A. Jasser2, Darin T. Lynch1, Mark D. Rollag4 and Frederick Zalatan1

1 Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York; 2 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania; 3 Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and 4 Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Requests for reprints: David E. Blask, Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, NY 13326. Phone: 607-547-3677;